Fecal Transplant

Treatment of Clostridium difficile

C. difficile , a spore-forming gram-positive anaerobe, is the most common infectious cause of antibiotic-associated diarrhea, ^, and its pathogenesis is primarily mediated by its toxin production. The most widely studied and reported use of FMT is in the treatment of refractory or recurrent CDI (rCDI). The incidence and morbidity associated with CDI among pediatric patients has been increasing over the past several years. ^, In addition, antibiotic resistance and resulting recurrent or chronic CDI are concomitantly increasing. ^, Although classically identified as a healthcare-associated infection, the rate of community-associated CDI has also increased in pediatric patients, with 70% to 80% of pediatric cases of CDI identified as community associated. ^, In fact, in contrast to adults, community-associated CDI is threefold more common than healthcare-associated CDI in children.

CDI is more common in children with complex medical conditions. In a large pediatric database including more than 4000 pediatric patients with a diagnosis of CDI, at least two-thirds had one or more complex chronic conditions. Adults and children with inflammatory bowel disease (IBD), for example, have rates of CDI that far exceed those seen in the general population. ^, A statewide database of hospital discharges in Maryland from 2009 to 2012 demonstrated a prevalence of CDI in children with IBD to be 46 per 1000 versus 4.1 per 1000 in children without IBD ( P < .001). In addition, children with cancer account for 25% of pediatric CDI. Fortunately, significant morbidity associated with CDI is less common in children than adults. Severe CDI-related complications, including toxic megacolon, perforation, and the need for a surgical intervention, occurred in fewer than 2% of pediatric patients with CDI. ^,

Fecal transplantation has been performed, reported, and studied in hundreds of adult patients with chronic CDI. Meta-analysis of case reports and clinical trials have demonstrated that more than 90% of patients with rCDI who have failed multiple courses of antibiotics can be cured with a single FMT. ^, In the first randomized controlled trial of FMT for rCDI, van Nood et al. reported on 16 adult subjects who underwent donor feces infusion via a nasoduodenal (ND) tube. Of those 16 subjects, 13 had resolution of symptoms after one infusion. The first pediatric case report was published by Russell et al. in 2010. He reported on the successful treatment of rCDI in a 2-year-old girl using donor feces infused via a nasogastric (NG) tube. A 2017 review of randomized controlled trials (RCTs) comparing FMT with vancomycin for rCDI found that statistically, FMT was significantly more effective (relative risk [RR] = 0.41, 95% confidence interval [CI]: 0.22 to 0.74; number needed to treat [NNT] = 3, 95% CI: 2 to 7).

All controlled FMT studies performed to date have been in adults, and there have been no controlled studies performed in pediatric patients with rCDI requiring FMT. However, small case series and isolated case reports have demonstrated similar FMT success rates in pediatric rCDI. This has been observed regardless of the mode of delivery and even in immunocompromised children. ^{, ,} The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) FMT Special Interest Group presented results from a multicenter retrospective review of pediatric patients with rCDI and demonstrated that FMT was successful in 272 of 336 (81%) patients after a single delivery. The success rate approached 90% when patients who received a second FMT were included in the analysis.

Although the mechanism of action of FMT is far from clear, it is proposed that restoring the intestinal microbiota to a prior, healthier state helps to counterbalance the CDI. In fact, however, it is unclear what components of stool play a role in helping eradicate the infection. Studies involving both specific bacterial combinations and, surprisingly, even nonbacterial components of the stool have also effectively treated rCDI.

Fecal Microbiota Transplantation Procedure

Donor/Recipient Screening

The FDA regulation and recommendations for donor screening continue to evolve, and as such it is recommended that practitioners performing FMT routinely check the FDA website for the most up-to-date guidance ( http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm ).A summary of their suggestions is that potential donors should undergo initial screening using a questionnaire similar to that provided to blood donors (AABB Donor History Questionnaire Documents are available at http://www.aabb.org/tm/questionnaires/Pages/dhqaabb.aspx ). It is also recommended that a follow-up questionnaire or assessment be performed at the time of donation, to screen for potential interval changes. Other suggested exclusion criteria are related to the content of the stool, such as a potential allergen, as well as medical conditions that may influence the gut microbiome. Such medical conditions include neurologic/neuropsychiatric disorders, metabolic disorders, gastrointestinal disorders, obesity, chronic proton pump inhibitor (PPI) use, malignancy, and recent antibiotic use, to name some.

Recommended testing from the JSCR to the FDA can be found in Table 93.1 . Other authorities have made additional recommendations for donor testing, including more comprehensive testing for infectious agents in the donor stool. Informed consent should include the potential risk of transmission of infectious agents.